MicroRNA expression profiling in type 2 diabetes patients treated with liraglutide

Type 2 diabetes (T2D) is a chronic metabolic condition characterized by impaired blood glucose regulation. Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is a commonly used drug for T2D management. Despite scientific advancements, the molecular mechanism underlying liraglutide therapy in T2D remains poorly understood. The study aimed to identify key microRNAs (miRNAs) and uncover the mechanisms of action of liraglutide in T2D by employing an integrated systems biology approach. The miRNA expression dataset, GSE223538, containing data from T2D patients treated with and without liraglutide, was retrieved from NCBI’s Gene Expression Omnibus (GEO) database. The dataset comprised 32 samples (13 control and 19 treated). Raw FASTQ reads were processed by trimming 3’ adapter sequences using the fastx_clipper tool from the FASTX-Toolkit. Reads shorter than 18 nucleotides were discarded, and the remaining reads were consolidated into unique sequences for streamlined mapping and analysis. Five miRNAs – hsa-miR-9-5p, hsa-miR-22-3p, hsa-miR-19b-3p, hsa-miR-132-3p and hsa-miR-93-5p – were found to be significantly linked to genes involved in the PI3K/Akt, MAPK, and FOXO1 signaling pathways. These findings suggest that liraglutide’s therapeutic effects may be mediated through miRNA-regulated mechanisms that modulate PI3K/Akt and other associated signaling pathways. In turn, these pathways regulate the cellular processes that enhance β-cell function, promote insulin secretion, and increase glucose uptake in patients with T2D. The results indicate that these miRNAs provide important insights into the mechanisms through which liraglutide reduces T2D risk, potentially guiding the approach for the development of novel biomarkers, targeted therapies, and precision health strategies. Additionally, the findings lay the groundwork for further experimental substantiation of the key pathways involved in liraglutide therapy.